The development of highly optimized chemical processes requires sophisticated analytical techniques to distinguish between optimum reactants, conditions and catalysts. These analytical techniques must be fast as well as accurate to deal with an increasing amount of data associated with the optimization. Gas chromatography in particular is widely used to assess the composition of products from chemical processes, but generally is slower than the tests used to effect chemical reactions. Combinatorial chemistry, in particular, provides a large number of samples to be analyzed in order to draw conclusions.
Combinatorial chemistry enables the formation of a large number of products from a relatively smaller number of precursors, thus facilitating the rapid comparison of a variety of methods, materials and products. This technique has become essential in the field of drug discovery, enabling the synthesis of large libraries of organic molecules for evaluation. More recently, combinatorial methods have been applied to the synthesis of chemical compounds and evaluation of libraries of catalytic materials and conditions for such syntheses. Developments in combinatorial chemistry thus have effected a need for high-speed analytical methods to carry out such evaluations.
An early illustration of the principle of combinatorial chemistry and associated analyses in chemical syntheses is U.S. Pat. No. 3,431,077, which discloses an analytical apparatus comprising a plurality of chambers containing test materials and connected by a relatively short passage to a chromatographic column. U.S. Pat. No. 4,099,923 teaches an automatic catalyst screening unit comprising a plurality of reaction chambers communicating via a common manifold with an analyzing means which sequentially analyzes product from each of the plurality of reactors; analysis of the reaction product may be effected by a gas chromatograph. WO 01/44801 A2 discloses testing of a plurality of catalysts using combinatorial chemistry wherein each of the catalyst beds is fluidized, and each of the effluents is analyzed to determine its chemical composition with chromatography being a preferred method of analysis.
The problem of rapidly screening large numbers of samples by liquid chromatographic techniques requiring up to an hour for each sample is recognized in U.S. Pat. No. 6,491,816 B2, which teaches parallel chromatographic columns with staggered parallel separation. U.S. Pat. No. 4,007,626 teaches chromatographic analysis of the volatile components in a sample having both volatile and nonvolatile components by vaporizing the sample, passing the vapor through a first chromatographic column to separate the constituents to be determined, and analyzing such constituents in a second chromatographic column while backflushing the first chromatographic column. High-throughput screening of catalysts using gas chromatography is addressed in U.S. Publication 2002/0014106 A1, through the use of highly parallel gas chromatographs (four or more columns) and microdetector arrays integrated with parallel reactors. In a situation wherein only the more volatile components of a sample are of interest, U.S. Pat. No. 5,057,126 discloses sequential injection of the sample into hot and lower-temperature vaporization chambers containing packing material, with the more volatile relevant components passing to a chromatographic column with the vaporization chambers being backflushed. U.S. Pat. No. 5,933,357 teaches a dual column gas chromatography system including a precolumn followed by a separating column and a method of establishing the retention times of components eluting from the partitioning in order to determine the optimum backflush point. The use of a backflushed precolumn to remove non-volatile material from samples prior to gas chromatography is taught by Gunnar Hagman and Johan Roeraade in “Online liquid backflush of an uncoated precolumn for automated gas chromatographic analysis of complex mixtures,” Journal of Chromatography A, 654 (1993), 287–298.
The art does not suggest, however, a method for expediting the analysis of all relevant components in a sample containing both low-boiling and high-boiling components.